INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Cell cholesterol removal by discoidal HDL: Influence of apolipoprotein A-I helix registry
Autor/es:
CUELLAR LA; CABALEIRO LV; PRIETO ED; GONZALEZ MC; GARDA HA
Lugar:
Puerto Madryn, Chubut
Reunión:
Congreso; 46th Annual Meeting Argentine Society for Biochemistry and Molecular Biology XLVI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2010
Institución organizadora:
Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)
Resumen:
<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:ES-AR; mso-fareast-language:ES;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Discoidal high-density lipoproteins (dHDL) are key intermediates in apolipoprotein A-I (apoAI) mediated cell lipid efflux. Due to the difficulty of dHDL isolation, the current knowledge about these complexes comes from studies using dHDL reconstituted by detergent dialysis, although they can also be generated by the spontaneous reaction of apoAI with phospholipid vesicles at their phase transition temperature, a procedure that may be similar to the "in vivo" apoAI lipidation. We show evidence that spontaneously generated dHDL are more active than those obtained by cholate-dialysis in promoting cholesterol efflux from murine macrophagues. Moreover, through FRET measurements with single tryptophan or fluorescent-labeled cysteine mutants of apoAI, it is detected that spontaneously generated dHDL consist predominantly of a unique apoAI configuration with a fix helix registry (LL5/2) in opposition to cholate-dialysis generated dHDL which consist of at least two configurations of variable helix registry (LL5/5 and LL5/2). Thus, our data indicate that only dHDL containig the LL5/2 configuration promote cell cholesterol efflux. As we previously proposed, the central 3-4 helix pairs form an intermolecular membrane-inserting bundle, which is possible in LL5/2 but not in LL5/5 configuration. Therefore, the formation of this intermolecular bundle should be essential for the dHDL activity